Major Announcement! FrCas9 Granted US Patent Authorization

The GeneRulor team’s self-developed DNA editing system, CRISPR-FrCas9, has officially been granted a patent by the United States Patent and Trademark Office (USPTO) (Application No.: 17676546). This milestone follows successful patent grants in Australia, Russia, Macau, and China, representing a significant breakthrough in overseas patent deployment for a Chinese company independently developing a foundational CRISPR-Cas9 system. GeneRulor holds exclusive rights to this patent.

US Patent Grant Notification

FrCas9 US Patent Publication

01 US Patent Grant — A Testament to Strength

The CRISPR-Cas9 gene editing system is currently one of the most widely used gene editing tools worldwide. However, the most commonly applied SpCas9 faces a critical issue: off-target effects. Such side effects may induce unintended gene mutations or even trigger oncogenesis, severely limiting its use in basic research and clinical applications. Although numerous studies have attempted to improve SpCas9’s targeting accuracy in recent years, they often come at the cost of editing efficiency. Additionally, SpCas9 is constrained by overseas patent barriers, restricting commercial activities and the development of gene therapy pipelines.

Against this backdrop, GeneRulor recognized that developing an independently owned foundational gene editing tool was essential. After decades of focus in the gene editing field, leveraging large-scale genome mining, bioinformatics prediction, PAM identification, cleavage activity assays, and off-target detection, the team developed the FrCas9 gene editing system.

FrCas9 is currently known for:

• Comparable cleavage efficiency to SpCas9

• Minimal off-target effects

• Broad PAM recognition

These features significantly enhance the effectiveness and precision of gene editing, making FrCas9 a preferred tool for both basic research and gene therapy. The results have been published in Nature Communications under the title: “FrCas9 is a CRISPR/Cas9 system with high editing efficiency and fidelity.”

The successful development of FrCas9 not only highlights GeneRulor’s technological capability but also strengthens its influence and recognition in the gene editing tool development field. Moving forward, GeneRulor remains committed to developing additional next-generation CRISPR systems.

Figure 1. Development of the FrCas9 Gene Editing System

02 Newly Upgraded eFrCas9 Debuts

As a technology-platform company in the gene editing field, GeneRulor not only possesses a series of independently patented gene editing tools but also continuously iterates and optimizes these tools. To explore the molecular mechanisms underlying FrCas9’s high cleavage efficiency and fidelity, we successfully captured and resolved the FrCas9-sgRNA-DNA ternary complex using cryo-electron microscopy (cryo-EM). The structural data revealed the interactions between FrCas9 and sgRNA-DNA, the PAM recognition mechanism, and the stability of the R-loop structure.

Based on these structural insights, we rationally evolved native FrCas9 via site-directed mutagenesis and multiple rounds of design and screening, ultimately developing the eFrCas9 gene editing system, achieving synergistic enhancement of editing efficiency and fidelity. This research has been submitted to an internationally renowned journal and has also been granted domestic patent protection — marking another major breakthrough in gene editing technology for GeneRulor.

Advantages of the eFrCas9 evolved system:

• Higher editing efficiency: Combining protein evolution with sgRNA optimization, achieving a two-fold increase in editing efficiency, significantly exceeding SpCas9.

• Higher specificity: Building upon the already low off-target effect, fidelity is further improved, greatly ensuring safety for clinical applications.

• Expanded applications for Base Editing and Prime Editing: Compatible with additional gene editing technologies, applicable in both basic research and clinical therapy.

• 

Figure 2. Evolutionary Optimization of eFrCas9

Figure 3. Patent Certificate

03 Patent Licensing & Collaboration — Inquiries Welcome

In December 2023, the FDA approved Casgevy (exa-cel), the first CRISPR-based gene editing therapy, marking the entry of CRISPR technology into the pharmaceutical stage and signaling a new era for gene editing. GeneRulor has deployed patents for FrCas9 across multiple countries worldwide, laying a solid foundation for applications in scientific research, crop breeding, in vivo and ex vivo gene therapy development, and establishing GeneRulor’s leading position in China’s gene editing and therapy development landscape.

Currently, GeneRulor has entered several domestic licensing collaborations:

• Commercial applications: ISO9001 quality management system established; open for partnerships for domestic and international sales promotion.

• Gene therapy applications: FrCas9 is applicable across multiple disease areas; strategic collaborations with pharmaceutical companies, biotech firms, and research institutions are welcome to jointly expand FrCas9’s applications.

• Regulatory support: GeneRulor has extensive experience in drug filings, assisting partners with regulatory submissions and clinical approval processes.

We look forward to collaborating and jointly leading the future of gene editing!